中国食管癌高发区食管癌前病变分布特征及其进展规律研究

发布时间：2017-12-27 09:25

本文关键词：中国食管癌高发区食管癌前病变分布特征及其进展规律研究　出处：《北京协和医学院》2016年硕士论文　论文类型：学位论文

【摘要】：研究目的基于河南林州、河北磁县和山东肥城三个食管癌早诊早治示范基地内镜筛查项目,描述我国食管癌高发区食管癌及其癌前病变分布、进展、发病/死亡规律,为制定不同级别癌前病变检出率参考值范围及随诊间隔,优化现行食管癌早诊早治项目技术方案提供科学依据。材料与方法本研究为基于自然人群的多中心横断面研究。依托我国食管癌高发区河南林州、河北磁县、山东肥城2005年-2009年完成筛查的自然人群队列,选择40-69岁使用内镜下碘染色及指示性活检技术进行筛查并有明确病理学诊断的筛查者为研究对象,回顾性整理其病理诊断结果。计算内镜筛查依从性,χ2检验比较食管癌及其癌前病变性别、地区、年龄分布差异,采用95%CI值分析食管癌及其癌前病变检出率范围。以2005-2009年进行内镜筛查、有明确病理诊断且未经过治疗的食管癌及其癌前病变患者为研究对象,进行二次内镜随访。计算两次内镜时间间隔,并比较前后两次内镜病理诊断结果,计算每年各级别癌前病变累积进展例数及累积进展概率,并进行性别、年龄别累积进展概率的比较。收集整理筛查覆盖人群发病、死亡等终点结局资料,采用趋势x2检验计算每一年不同级别病理诊断者累计发病、死亡率；x2检验比较各级别病理诊断研究对象中,不同性别、年龄别间发病率、死亡率的差别;对轻度不典型增生者3年累计发病率与其他每年累计发病率比较；对中度不典型增生者1年累计发病率与其他每年累计发病率比较。研究结果1.本研究覆盖人群99060人,其中40-69岁人群46568人,首次参与内镜筛查人数为21955人,内镜筛查顺应性为47.15%。其中女性(50.91%,11739/23058)依从性高于男性(43.45%,10216/23510)(x2=47.15,P0.001)。排除活检组织过小不足以诊断191人,共计21764人纳入本研究。食管病变检出率为24.65%(5365/21764)。其中基底细胞增生1729例(7.94%,95% CI：7.59%-8.30%),低级别上皮内瘤变3163例(14.53%,95%CI：14.06%-15.00%),高级别上皮内瘤变335例(1.54%,95%CI：1.38%-1.70%),食管癌138例(0.63%,95%CI：0.53%-0.74%)。检出率从高到低依次为：低级别上皮内瘤变基底细胞增生高级别上皮内瘤变食管癌。在食管癌及各级癌前病变中,男性检出率均显著高于女性。基底细胞增生男、女检出率分别为9.05%和6.98%(x2=19.438,P0.001)；低级别.上皮内瘤变男、女检出率分别为15.85%和13.38%(x2=26.661,P0.001)；高级别_上皮内瘤变男、女检出率分别为1.74%和1.37%(x2=4.865,P=0.027)；食管癌男、女检出率分别为0.85%和0.45%(x2=13.829,P0.001)。基底细胞增生、低级别上皮内瘤变、高级别上皮内癌变和食管癌检出率均有随年龄增加而增加的趋势,趋势x2检验均有统计学意义。40～44岁调查对象各级别癌前病变检出率最低,分别为7.61%(425/5585)、6.70%(374/5585)、0.34%(19/5585)和0.18%(10/5585)；65-69岁调查对象分别为8.14%(84/1093)、21.87%(239/1093)、3.84%(42/1093)和1.92%(21/1093)。并且在每一个年龄组中,检出率由高到低均为低级别上皮内瘤变基底细胞增生高级别上皮内瘤变食管癌。林州、磁县、肥城三地各级食管癌前病变检出率均不同,其差别有统计学意义；其中,基底细胞增生检出率磁县最高,为18.57%(1136/6116).低级别上皮内瘤变和高级别上皮内瘤变检出率均为林州最高,分别为17.40%(1787/10269)和1.80%(185/10269)。三地食管癌检出率差别无统计学意义(Z2=0.613,P=0.736)。2.2005-2009年进行内镜筛查的人群共21955人,在9年里共计随访2389人,内镜筛查依从性为10.88%,其中男性内镜筛查依从性为11.26%,女性内镜筛查依从性为10.55%,二者差别无统计学意义(x2=0.096,P=0.099)。三个食管癌早诊早治示范基地二次内镜筛查依从性均较低,其中,林州二次内镜筛查依从性最高,为15.81%,磁县二次内镜筛查依从性最低,仅为4.5%。在随访的前七年,中度不典型增生累积进展率始终高于轻度不典型增生；随访第七年开始,二者累积进展率交叉。对于轻度不典型增生,2-4年累积进展率由0.18%进展为1.07%,累积进展率较低,且变化幅度不大,到第5年及以后每年进展率加快,均增长1个百分点以上；对于中度不典型增生,2-4年累积进展率较高,为3.33%-3.59%,但变化幅度不大,4-5年由3.59%进展为4.62%；对于低级别上皮内瘤变,也有类似上述轻度不典型增生和中度不典型增生的规律。男性中度不典型增生随访2-9年累积进展率(5.29%-10.58%)始终大于轻度不典型增生(0.18%-7.18%)；女性中度不典型2-4年累积进展率高于轻度不典型增生,5年之后低于轻度不典型增生。各年龄组中,在随访最初,中度不典型增生累积进展率均显著高于轻度不典型增生,随后该差异逐渐减小,40-49岁组在随访第7年、50-59岁组在随访第8年,轻度不典型增生累积进展率开始高于中度不典型增生。3.在我国食管癌高发区,内镜筛查并随访10年后,各级别病理诊断研究对象食管癌累计发病率/死亡率均呈上升趋势,趋势卡方检验均有统计学意义。在每一年中,发病率/死亡率大小均为中度不典型增生轻度不典型增生基底细胞增生正常。男性食管癌累计发病率/死亡率高于女性；食管癌累计发病率／死亡率随年龄增加而增加。轻度不典型增生3年累计发病率与1-6年累计发病率比较,无显著差异,(P0.05),直至第7年,二者比较差异有统计学意义(x2=5.286,P=0.021)；中度不典型增生1年累计发病率与2-4年累计发病率比较,无显著差异(P0.05),直至第5年,二者比较差异有统计学意义x2=11.465,P=0.001。结论我国食管癌高发区自然人群中存在大量无症状癌前病变及癌症患者,癌前病变检出率与年龄、性别密切相关,高发区早诊早治应进一步加强健康教育和组织发动,进一步提高癌前病变检出率,尤其应提高男性以及高年龄筛查对象参加筛查依从性避免癌前病变漏诊,从而提高筛查效果。中度不典型增生累积进展率及食管癌发生、死亡风险均高于轻度不典型增生。中度不典型增生累积进展率及食管癌发病、死亡率4年内变化不大,轻度不典型增生累积进展率及食管癌发病、死亡率5年内变化不大,建议对中度不典型增生3-4年进行一次随访,轻度不典型增生患者每5-6年进行一次随访。
[Abstract]:Based on the purpose of early diagnosis in Henan Linzhou, Hebei Cixian and Shandong Feicheng three esophageal cancer early treatment demonstration base of endoscopic screening project, described China's high incidence area of esophageal cancer esophageal cancer and its precancerous lesion distribution, pathogenesis, progress / death rules for different levels of precancerous lesions and the detection rate of the reference value range and follow-up interval optimization of early diagnosis of esophageal cancer, the early treatment project technical solutions and provide scientific basis for. Materials and methods this study was a multicenter cross-sectional study based on natural populations. Relying on China's high incidence area for esophageal cancer in Linzhou, Henan, Hebei Cixian, Shandong Feicheng in 2005 -2009 years to complete the screening queue natural population, aged 40-69 years old were chosen using iodine staining under endoscopy and biopsy technique for screening and definite pathological diagnosis screening as the research object, retrospectively collected the pathological diagnosis results. The compliance of endoscopic screening was calculated. Chi square test was used to compare the difference of sex, region and age distribution between esophageal cancer and precancerous lesion. The 95%CI value was used to analyze the detection rate of esophageal cancer and its precancerous lesions. The 2 groups were compared. The endoscopic screening, pathological diagnosis and treatment of esophageal cancer and precancerous lesions in 2005-2009 years were carried out in two patients. The time interval between the two endoscopic intervals was calculated, and the endoscopic diagnostic results were compared before and after two times. The cumulative progression rate and cumulative progress probability of precancerous lesions at various levels were calculated annually, and the cumulative progress probability of gender and age was compared. Collect the death incidence and population screening cover end point outcome data using the trend, calculated by x2 test every year, different levels of pathologic diagnosis, the cumulative incidence of mortality; x2 test comparing the level of pathological diagnosis study in different gender and age between the incidence rate and death rate difference; for mild dysplasia in 3 year cumulative incidence compared with other year cumulative incidence of moderate dysplasia; 1 year cumulative incidence compared with other year cumulative incidence. Results of the study, 1. subjects covered 99060 people, of which 46568 were 40-69 years old, and 21955 were screened for the first time in endoscopic screening and 47.15% for endoscopic screening. The compliance of women (50.91%, 11739/23058) was higher than that of men (43.45%, 10216/23510) (x2=47.15, P0.001). The removal of biopsy tissue was not enough to diagnose 191 people, and a total of 21764 people were included in this study. The detection rate of esophageal lesions was 24.65% (5365/21764). Basal cell hyperplasia was seen in 1729 cases (7.94%, 95% CI:7.59%-8.30%), low grade intraepithelial neoplasia in 3163 cases (14.53%, 95%CI:14.06%-15.00%), high-grade intraepithelial neoplasia in 335 cases (1.54%, 95%CI:1.38%-1.70%), and esophageal cancer in 138 cases (0.63%, 95%CI:0.53%-0.74%). The rate of detection is from high to low in the following order: low grade intraepithelial neoplasia and high grade intraepithelial neoplasia of esophagus. In the esophageal cancer and the precancerous lesions at all levels, the male detection rate was significantly higher than that of the female. Basal cell hyperplasia of male and female detection rates were 9.05% and 6.98% (x2=19.438, P0.001); low level. Male and female detection rates were 15.85% and 13.38% intraepithelial neoplasia (x2=26.661, P0.001); high grade intraepithelial neoplasia _ male and female detection rates were 1.74% and 1.37% (x2=4.865, P=0.027) esophageal cancer; male and female detection rates were 0.85% and 0.45% (x2=13.829, P0.001). The detection rates of basal cell proliferation, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia and esophageal cancer all increased with age. The trend of x2 test was statistically significant. At the age of 40~44, the detection rate of precancerous lesions at all levels was the lowest, which were 7.61% (425/5585), 6.70% (374/5585), 0.34% (19/5585) and 0.18% (10/5585) respectively, and 65-69 years old subjects were 8.14% (84/1093), 21.87% (239/1093), 3.84% (42/1093) and 1.92% (21/1093), respectively. And in each age group, the detection rate was from high to low to low grade intraepithelial neoplasia and high grade of intraepithelial neoplasia. Linzhou, Cixian, Feicheng and three levels of esophageal precancerous lesion detection rate were different, the difference was statistically significant; the basal cell hyperplasia detection rate of Cixian is the highest, was 18.57% (1136/6116). Low grade intraepithelial neoplasia and high grade intraepithelial neoplasia detection rate was highest in Linzhou, were 17.40% (1787/10269) and 1.80% (185/10269). There was no significant difference in the detection rate of three esophageal carcinoma (Z2=0.613, P=0.736). A total of 21955 people screened for endoscopy in 2.2005-2009 were enrolled in the past 9 years. 2389 patients were followed up for 9 years. The adherence of endoscopic screening was 10.88%, of which 11.26% of male endoscopy screening and 10.55% of female endoscopic screening were not statistically significant (x2=0.096, P=0.099). Three esophageal cancer early diagnosis and treatment demonstration base two endoscopic screening compliance is relatively low, of which Linzhou two endoscopic screening compliance is the highest, 15.81%, Cixian two endoscopic screening compliance is the lowest, only 4.5%. In the first seven years of follow-up, the cumulative progression rate of moderate atypical hyperplasia was always higher than that of mild atypical hyperplasia; after seventh years of follow-up, the cumulative rate of progress of the two was cross. For mild dysplasia, 2-4 year cumulative progress rate from 0.18% in 1.07%, the cumulative progress rate is low, and the change is not obvious, to the fifth year and later progress rate, average growth of more than 1 percentage points; for moderate dysplasia, 2-4 year cumulative progress rate is higher, but the change rate is 3.33%-3.59%, little 4-5 by the 3.59% progress is 4.62%; for low grade intraepithelial neoplasia, also have similar mild dysplasia and moderate dysplasia of the law. Male moderate atypical hyperplasia followed up for 2-9 years. The cumulative progression rate (5.29%-10.58%) was always higher than that of mild atypical hyperplasia (0.18%-7.18%). The cumulative progression rate of female moderate atypical 2-4 years was higher than that of mild atypical hyperplasia, and 5 years later, it was lower than mild atypical hyperplasia. In all age groups, the cumulative progression rate of moderate atypical hyperplasia was significant at the beginning of the follow-up.
【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R735.1

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